bluuebunny/crossref_metadata_2025_split huggingface dataset:
Test-reduced teaching for stimulation of intrinsic motivation (TRUST): a randomized controlled intervention study
Authors: Faure Theresa , Weyers Imke , Voltmer Jan-Bennet , Westermann Jürgen , Voltmer Edgar 
Published: July 2024

Abstract
Background
The anatomy dissection course is a major part of the first two years of the traditional medical curriculum in Germany. The vast amount of content to be learned and the repeated examination is unanimously perceived by students and teachers as a major stress factor that contributes to the increase of psychosocial stress during the first two years of the course of study. Published interventions for specific stress reduction are scarce.

Methods
In a randomized, controlled design two intervention groups were compared with a control group (CG) over the whole dissection course (nine measuring points before, during and after first and second semester). The ‘Stress Management intervention (IVSM)’ targeted at the setting of personal standards, the ‘Friendly Feedback intervention (IVFF)’ at the context of frequent testing. Quantitative surveys were distributed at nine measuring points. The questionnaire comprised validated instruments and self-developed items regarding stress, positive and negative affect, anxiety, intrinsic and extrinsic motivation, self-efficacy, and perceived performance.

Results
Out of 195 students inscribed in the dissection course, 166 (85%) agreed to participate in the study. The experience of stress during the dissection course was significantly higher in the CG than in the IVFF. Anxiety and negative affect were lower in students of the IVFF while positive affect, intrinsic motivation, and self-efficacy were higher than in the CG. For anxiety and negative affect in the IVSM this was especially seen at the end of the second semester. The self-perceived increase in both knowledge and preparedness for the first big oral and written examination did not differ between the study groups. About three quarters of the participants would choose the intervention ‘Friendly Feedback’ if given the choice.

Conclusions
Replacing formal tests with friendly feedback has proven to be an effective measure to reduce stress and negative affect and foster positive affect, self-efficacy, and intrinsic motivation, while it did not impair self-perceived academic performance.
Carbohydrate antigen 125 on epicardial fat and its association with local inflammation and fibrosis-related markers
Authors: Eiras Sonia , de la Espriella Rafael , Fu Xiaoran , Iglesias-Álvarez Diego , Basdas Rumeysa , Núñez-Caamaño J. R. , Martínez-Cereijo J. M. , Reija L. , Fernández A. L. , Sánchez-López David , Miñana Gema , Núñez Julio , González-Juanatey José R. 
Published: July 2024

Abstract
Background
Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis.

Methods
Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively.

Results
The median age was 71 (63–74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels.

Conclusion
Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).

Graphical Abstract
Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
Authors: Kalra Jessica , Baker Jennifer , Sun XuXin , Kyle Alastair , Minchinton Andrew , Bally Marcel B. 
Published: July 2024

Abstract
Background
The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes.

Methods
Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-1mkate, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection.

Results
A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-1mkate models.

Conclusion
These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect.
Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body
Authors: Rosmus Dennis-Dominik , Koch Jana , Hausmann Annika , Chiot Aude , Arnhold Franz , Masuda Takahiro , Kierdorf Katrin , Hansen Stefanie Marie , Kuhrt Heidrun , Fröba Janine , Wolf Julian , Boneva Stefaniya , Gericke Martin , Ajami Bahareh , Prinz Marco , Lange Clemens , Wieghofer Peter 
Published: July 2024

Abstract
Background
The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive.

Results
In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood. We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia. Embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes.

Conclusion
Our study identifies hyalocytes as long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye. As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases. Therefore, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface.
Impaired ATP hydrolysis in blood plasma contributes to age-related neutrophil dysfunction
Authors: Ledderose Carola , Valsami Eleftheria-Angeliki , Elevado Mark , Liu Qing , Giva Brennan , Curatolo Julian , Delfin Joshua , Abutabikh Reem , Junger Wolfgang G. 
Published: July 2024

Abstract
Background
The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals.

Results
Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging.

Conclusions
Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.
Surgical treatment of atrial fibrillation in elderly patients undergoing high risk cardiac surgery
Authors: Uzzaman Mohammed Mohsin , Manoly Imthiaz , Pannikkar Mohini , Caruso Vincenzo , Matuszewski Maciej , Nikolaidis Nicolas , Billing Stephen 
Published: July 2024

Abstract
Background
Evaluating outcomes of concurrent Cox-Maze procedures in elderly patients undergoing high-risk cardiac surgery.

Mehods
We retrospectively identified patients aged over 70 years with Atrial Fibrillation (AF) from 2011 to 2017 who had two or more other cardiac procedures. They were subdivided into two groups: 1. Cox-Maze IV AF ablation. 2. No-Surgical AF treatment. A propensity match score was used to generate a homogeneous cohort and to eliminate confounding variables. Heart rhythm was assessed from Holter reports or 12-lead ECG. Follow-up data was collected through telephone consultations and medical records.

Results
There were 239 patients. Median follow up was 61 months. 70 patients had Cox-Maze IV procedures (29.3%). Demographic, intra- and post-operative outcomes were similar between groups although duration of pre-operative AF was shorter in Cox-Maze group (p = 0.001). There was no significant 30-day mortality difference in propensity matched cohorts (n = 84. P = 0.078). Sinus rhythm at annual and latest follow-up was 84.9% and 80.0% respectively in Maze group – 160 patients (66.9%) were alive at long-term follow-up with good survival outcomes in Cox Maze group. There was a high proportion of patients in NYHA 1 status in Cox-Maze group. No differences observed in freedom from stroke (p = 0.80) or permanent pacemaker (p = 0.33) between the groups.

Conclusions
Surgical ablation is beneficial in elderly patients undergoing high-risk surgery - promoting excellent long-term freedom from AF and symptomatic / prognostic benefits, without added risk. Therefore, surgical risk should not be reason to deny benefits of concomitant AF-ablation.

Clinical trial registration
Not required.
Long-term outcomes following mitral valve replacement in children at heart center Leipzig: a 20-year analysis
Authors: Schumacher Katja , Marin-Cuartas Mateo , Aydin Muhammed Ikbal , de la Cuesta Manuela , Meier Sabine , Borger Michael Andrew , Dähnert Ingo , Kostelka Martin , Vollroth Marcel 
Published: July 2024

Abstract
Background
Although mitral valve repair is the preferred surgical strategy in children with mitral valve disease, there are cases of irreparable severe dysplastic valves that require mitral valve replacement. The aim of this study is to analyze long-term outcomes following mitral valve replacement in children in a tertiary referral center.

Methods
A total of 41 consecutive patients underwent mitral valve replacement between February 2001 and February 2021. The study data was prospectively collected and retrospectively analyzed. Primary outcomes were in-hospital mortality, long-term survival, and long-term freedom from reoperation.

Results
Median age at operation was 23 months (IQR 5–93), median weight was 11.3 kg (IQR 4.8–19.4 kg). One (2.4%) patient died within the first 30 postoperative days. In-hospital mortality was 4.9%. Four (9.8%) patients required re-exploration for bleeding, and 2 (4.9%) patients needed extracorporeal life support. Median follow-up was 11 years (IQR 11 months − 16 years). Long-term freedom from re-operation after 1, 5, 10 and 15 years was 97.1%, 93.7%, 61.8% and 42.5%, respectively. Long-term survival after 1, 5, 10 and 15 years was 89.9%, 87%, 87% and 80.8%, respectively.

Conclusion
If MV repair is not feasible, MV replacement offers a good surgical alternative for pediatric patients with MV disease. It provides good early- and long-term outcomes.
Extent of magnitude representation deficit and relationship with arithmetic skills in children with 22q11.2DS
Authors: Favre Emilie , Piveteau Margot , Babinet Marie-Noelle , Demily Caroline 
Published: July 2024

Abstract
Background
Previous studies have produced conflicting results concerning the extent of magnitude representation deficit and its relationship with arithmetic achievement in children with 22q11.2 deletion syndrome. More specifically, it remains unclear whether deficits are restricted to visuospatial content or are more general and whether they could explain arithmetical impairment.

Methods
Fifteen 5- to 12-year-old children with 22q11.2 deletion syndrome and 23 age-matched healthy controls performed a non-symbolic magnitude comparison task. Depending on the trial, participants had to compare stimuli with high or low visuospatial load (visuospatial stimuli or temporal sequence of visual stimuli). The participants also completed a battery of arithmetic skills (ZAREKI-R) and a battery of global cognitive functioning (WISC-V or WPPSI-IV), from which working memory and visuospatial indices were derived.

Results
Children with 22q11.2DS responded as fast as healthy controls did but received fewer correct responses, irrespective of visuospatial load. In addition, their performance in the non-symbolic magnitude comparison task did not correlate with the ZAREKI total score, while the working memory index did.

Conclusion
Children with 22q11.2DS might suffer from a global magnitude representation deficit rather than a specific deficit due to visuospatial load. However, this deficit alone does not seem to be related to arithmetic achievement. Working memory might be a better concern of interest in favoring arithmetic skills in patients with 22q11.2 deletion syndrome.

Trial registration
Clinicaltrials, NCT04373226. Registered 16 September 2020.
Financial Toxicity in Cancer Supportive Care: An International Survey
Authors: Chan Alexandre , Ke Yu , Tanay Mary , Dagsi Mary , Bergerot Cristiane , Dixit Niharika , Eng Lawson , Cardeña Gutiérrez Ana , Jiang Changchuan , Velázquez Ana I. , Islami Farhad , Soto-Perez-de-Celis Enrique 
Published: July 2024

PURPOSE The study aims to explore unmet social needs and sources of financial toxicities in patients as noted by health care professionals and researchers in cancer supportive care, shedding light on potential health disparities. METHODS In this cross-sectional survey, we anonymously surveyed active members of the Multinational Association of Supportive Care in Cancer (MASCC). The survey, structured in three sections, included questions regarding the routine assessment of social needs during patient consultations, sociodemographic aspects, factors influencing financial toxicity (FT), perceived support for managing FT, and available/desirable resources. RESULTS A total of 218 MASCC members were included, predominantly from high-income countries (HIC, 73.4%), with many age 41-60 years (56.5%) and female (56.9%). Drug/treatment cost and insurance coverage were the main sources for FT among the HIC, whereas participants from low-middle–income countries (LMIC) considered transportation cost, loss of employment because of cancer diagnosis, and unavailability of return-to-work services as the top three sources of FT. Respondents from LMIC (adjusted odds ratio [aOR], 3.01 [95% CI, 1.15 to 7.93]) and physicians (aOR, 2.67 [95% CI, 1.15 to 6.21]) were more likely to routinely assess financial coverages. Socioeconomic status was consistently ranked as one of the top three sources of financial toxicities by participants from LMIC (34%), HIC excluding the United States (38%), those who do not self-identify as racial/ethnic minority (36%), and physicians (40%). CONCLUSION This global survey of health care professionals and researchers in HIC and LMIC revealed varying approaches to assessing financial coverage and social needs. Socioeconomic status emerged as a consistent concern across countries, affecting financial toxicities. The study highlights the need for tailored approaches and improved resource visibility while emphasizing clinicians' pivotal role in addressing financial aspects of cancer care.
Genomics to select treatment for patients (pts) with metastatic cancer: Final analysis of Molecular Tumor Board (MTB) evaluations in the ROME trial.
Authors: Botticelli Andrea , Scagnoli Simone , Conte Pierfranco , Cremolini Chiara , Ascierto Paolo Antonio , Cappuzzo Federico , Aglietta Massimo , Mazzuca Federica , Capoluongo Ettore , Blandino Giovanni , Malapelle Umberto , Nuti Marianna , D'Amati Giulia , Cerbelli Bruna , Pruneri Giancarlo , Biffoni Mauro , Giannini Giuseppe , Cognetti Francesco , Curigliano Giuseppe , Marchetti Paolo ,   ROME Trial Investigators
Published: July 2024

3157 Background: The ROME trial (NCT04591431) investigates the efficacy of a tailored treatment (TT), driven by extensive genomic tests and Molecular Tumor Board (MTB) evaluation, compared to standard treatment (SoC) in patients (pts) with refractory metastatic cancer. Here we report the prevalence of actionable variants identified and the personalized treatment received by the patients enrolled. Methods: A centralized extensive NGS test (FoundationOne CDx and Liquid CDx) was performed on both tissue and blood samples. Pts with at least one potentially targetable alteration matched to the available drugs were discussed at the MTB. MTB evaluation criteria were: genomic variant type, tumor mutational burden (TMB), VAF, availability of preclinical or clinical data of efficacy and patients’ clinical characteristics. COSMIC, ClinVar, OncoKB and VarSome datasets were used to evaluate the clinical actionability of genomic alterations. MTB indications were: randomization to TT vs SoC, screening failure (SF), or indication to other trial/access to the drug. Results: From November 2020 to August 2023, 1794 pts were screened. A total of 127 weekly MTB meetings were conducted and 899 cases were discussed (7 cases/meeting on average). After MTB discussion, a targetable genomic alteration was identified in 425 pts, who received an indication to be randomized. MTB assigned ICIs to 190 pts (155 to ipilimumab plus nivolumab; 8 to nivolumab) due to high (≥10 mut/mb) TMB. 234 pts had indications to target therapy: 86 pts (37%) to PI3K/AKT/mTOR inhibitors(i), 59 (25%) anti-HER2 agents, 34 (15%) FGFRi, 31 (13%) BRAF/MEKi, 7 (3%) PARPi, 5 (2%) CDK4/6i, 4 (2%) ALKi, 2 (>1%) NTRKi, 2 (>1%) RETi, 2 (>1%) Hedgehog-i, 1 (>1%) JAKi, 1 (>1%) MEKi. 27 pts had indication to ICIs plus target therapy combinations. Additionally, 150 pts with potentially hereditary variants were addressed to genetic counselling and germline testing. Finally, according to the genomic evaluation, 63 pts were referred by MTB to other clinical trial even if considered SF for the ROME trial, 34 patients received from the MTB a modification of the initially proposed standard therapy and 4 had both suggestions. Overall, 652 pts (36%) received an indication following NGS test and MTB evaluation. Conclusions: Our study provides evidence that MTB discussion of comprehensive genomic profiling data identifies a personalized treatment in a large (36%) fraction of patients, thus outperforming the traditional histological approach. Clinical trial information: NCT04591431 .